1. Field of the Invention
The present invention generally relates to a composition for treating hearing loss. More specifically, the present invention relates to a composition for treating hearing loss that includes components that function through different biological mechanisms and provide an additive effect that is greater than the effect of the most effective of the individual components alone, and a method of treating hearing loss including the step of administering the composition to a mammal prior to or within 3 days following trauma to the inner ear.
2. Description of the Related Art
Extensive studies have been performed on compositions for treating hearing loss, along with methods of treating hearing loss using various compositions. In particular, antioxidants, among numerous other components, have been found to play a role in the prevention of noise-induced hearing loss. Specific antioxidants shown to be partially effective in reducing noise-induced hearing loss in animal models include glutathione (GSH)/glutathione monoethyl ester, N-acetylcysteine (NAC), resveratrol, allopurinol, R-phenylisopropyladenosine, salicylates, and vitamins A, C, and E. Otoprotective effects of the above individual dietary antioxidants are well known in the art.
To date, little, if any, additive effects have been found to exist by combining many of the known components for treating hearing loss. Additive effects, as used herein, refer to effects that are greater than the most effective of the individual components alone. For the most part, no greater effect is observed by combining many of the different components that are effective in treating hearing loss than the effect of the most effective individual component in the composition, i.e., combinations of agents are only as effective as the most effective single agent delivered alone. For example, FIG. 1 shows the results of experimentation relative to additive effects of Trolox®, which is a water-soluble analogue of alpha-tocopheral (vitamin E), in combination with vitamins A and C, as compared to the effects of Trolox® alone. The experimental conditions are described in further detail in the Examples section below. As is evident from FIG. 1, the combined effect of Trolox® and vitamins A and C in minimizing threshold shift, i.e., hearing loss, is no greater than the effect of Trolox® alone. As such, the combination of Trolox® and vitamins A and C does not produce an additive effect in treating hearing loss.
As the understanding of the mechanisms by which the various antioxidants work to treat or prevent hearing loss has become clearer, it has been found that combinations of certain antioxidants that act via complementary, but different, biochemical mechanisms may be more effective than the individual antioxidants alone. However, given the volume and variety of components that are known to affect hearing loss, as well as lack of knowledge relative to specific mechanisms by which the components function, additive effects between components have not been recognized to date. Further, significant treatments for preventing hearing loss, specifically noise-induced hearing loss, using a post-trauma treatment paradigm have yet to be achieved. There has been a long-felt need for such a treatment, since the vast majority of treatments to prevent noise-induced hearing loss are needed post-trauma.
In spite of the fact that additive effects between various components have not been recognized to date, certain disclosures have been made that generally group together many components for treating hearing loss. These disclosures do not teach with sufficient specificity combinations of specific components that exhibit additive effects in treating hearing loss or which are effective in post-trauma treatment paradigms. For example, U.S. Pat. No. 6,093,417 is directed to a composition to treat ear disorders. The composition is topically applied into an ear canal to treat the hearing disorder. Although the U.S. Pat. No. 6,093,417 is directed to a composition that may include many components that are known to be somewhat effective in reducing hearing loss alone, including vitamin E and zinc salts, such as zinc salicylate, there is no recognition of an additive effect between any of the components, when applied topically. As is evident from FIG. 1, many combinations of components do not exhibit additive effects. As such, the random combination of agents disclosed in the U.S. Pat. No. 6,093,417 would not provide any greater effect for treating hearing loss if included in the composition. Furthermore, effectiveness of the individual components greatly varies between oral, intravenous, and topical administration, and compositions for treating hearing loss are formulated differently depending on the contemplated mode of administration. Finally, the U.S. Pat. No. 6,093,417 does not teach with sufficient specificity biologically effective amounts of each component that would be sufficient to produce an effect individually, let alone additive effects between the various components. Thus, the disclosure of the U.S. Pat. No. 6,093,417 patent provides no further teaching than what was already known about each of the components, i.e., that each component, when used individually, is modestly effective in preventing hearing loss.
The use of vitamin E alone, in biologically effective amounts, has been disclosed for treating noise-induced hearing loss. More specifically, Hou et al., Effects of alpha-tocopheral on noise-induced hearing loss in guinea pigs, Hear Res. 179:1-8 (2003), discloses treatment of acoustical over-stimulation with 10 to 50 mg/kg of alpha tocopheral. Further, the use of salicylates, in biologically effective amounts, has also been disclosed for treating hearing loss. More specifically, Kopke et al., Reduction of noise-induced hearing loss using L-NAC and salicylate in the chinchilla, Hear Res. 149: 138-146 (2000), discloses treatment of noise-induced hearing loss with 50 mg/kg of salicylate twice daily. However, none of the prior art suggests combining vitamin E or a salicylate in biologically effective amounts, and none of the prior art recognizes any type of additive effect that may be achieved with such a combination, or an ability to administer a combination of vitamin E and a salicylate post-trauma with excellent results for which, as set forth above, there has been a long-felt need. Furthermore, the fact that other similar combinations of components do not produce an additive effect, as shown in FIG. 1, illustrates that such additive effects would not be expected.
Although many of the components that are used to treat or prevent hearing loss provide other beneficial functions and are included in multivitamins, known multivitamins likewise do not include salicylates or biologically effective amounts of the components sufficient to treat or prevent hearing loss. Furthermore, multivitamins are generally used as part of a regular dietary regimen and there is no data that suggests the use of multivitamins that include a specific combination and concentration of components to prevent hearing loss induced by noise or other stress.
Thus, there is an opportunity to provide a composition and a method of treating hearing loss including the step of administering the composition that includes a specific combination of components having an additive effect that is greater than the effect of the most effective of the individual components alone in treating hearing loss when used in biologically effective amounts, and that is effective even when first administered as late as 3 days post-trauma.